Identification of Candidate Genes Involved in the Etiology of Non-Syndromic Cleft Lip with or without Cleft Palate and Isolated Cleft Palate. Summary of the Doctoral Thesis

Abstract

Cleft lip with or without cleft palate and isolated cleft palate (CL/CLP/CP) is one of the most common birth defects worldwide with prevalence of approximately 1 in 700 live births in European populations. Individuals with CL/CLP/CP need multidisciplinary care from birth to adulthood even after surgical repair. CL/CLP/CP affects speech, dental development, hearing, appearance and psychology of person. It has been considered that individuals with this malformation have higher morbidity and mortality of cardiovascular diseases and cancers if compared to unaffected individuals. Despite possibility of surgical repair, this defect remains important health and social problem in nowadays. Formation of orofacial clefts is a result between interaction of environmental and genetic factors. Recent estimates suggest that 2-14 genes could be involved in the formation of CL/CLP/CP. In present study we performed case-control analysis and family based association test in CL/CLP and CP patients, their parents and control group. Identification of possible candidate genes involved in the etiology of non-syndromic cleft lip with or without cleft palate and isolated cleft palate in Latvian population was the objective of the present study. Our results showed very strong association between FGFR1, WNT3, SKI, BMP4 and IRF6 genes and non-syndromic CL/CLP and CP and possible interaction between 19q13 locus and non-syndromic CL/CLP, which continue to support the involvement of these genes in the development of non-syndromic clefts in Caucasians. Results of this study is step further of understanding of this complex malformation and estimating the impact of genes involved in the etiology of non-syndromic cleft lip with or without cleft palate and isolated cleft palate.